Pathological diagnosis
Mixed germ cell tumors composed of
teratoma, yolk sac tumor, embryonal
carcinoma, and rare
syncytiotrophoblast cells
Gonad
Germ cell + sex cord-stromal cells
Sex cord-stromal cells
Testis: Sertoli cells, Leydig cells
Ovary: granulosa cells, theca cells
Germ cell-sex cord stromal tumor
Gonadoblastoma
Unclassified type
Germ cell tumors
Intratubular germ cell neoplasia, unclassified
seminoma: classical or spermatocytic
Non-seminomatous germ cell tumors:
embryonal carcinoma
teratoma: mature or immature
yolk sac tumor
choriocarcinoma
Histogenesis of germ cell tumors (1)
Two divergent pathways:
seminomaembryonal carcinoma
--->other germ cell tumors
questions:
seminoma with nonseminomatous metastasis
( autopsy findings )
seminoma with nonseminomatous GCTs
differentiation and/or elevated AFP/hCG
Histogenesis of germ cell tumors (2)
Tetrahedron model of histogenesis
Ultrastruct Pathol 1988; 12:67-86
revised tetrahedron model of histogenesis
Diagnostic surgical pathology, Testicular and
paratesticular neoplasms. 1994:1885-1947
Mixed germ cell tumors (1)
definition
Neoplasms contain more than one germ
cell tumor component. Cases of
seminoma with syncytiotrophoblasts
cells are, by convention, excluded from
this category.
Mixed germ cell tumors (2)
general features
Incidence:
32% of testicular GCTs ( in 1053 cases )
60% of testicular GCTs ( in 513 cases )
91% of nonseminomatous GCTs (in 513 cases)
A common pattern is embryonal carcinoma
with one or more components of teratoma,
seminoma, and yolk sac tumor, but virtually
any combination can be seen.
Mixed germ cell tumors (3)
clinical features
Symptoms:
testicular enlargement
sometimes associated with pain
average age: 30 years old
serum marker elevations are common:
AFP ( 60% in metastatic cases )
hCG ( 55% in metastatic cases )
Mixed germ cell tumors (4)
treatment of NSGCT
Tumor limited to the testis: controversial
retroperitoneal LN dissection ( RPLND )
RPLND(-): F/U
relapse on F/U ( 10% ): cisplastin-base C/T
>98% cure rate
RPLND(+):
F/U or C/T depending on patient/tumor conditions
98-100% survival
Mixed germ cell tumors (5)
treatment of NSGCT
Tumor limited to the testis: controversial
simple conservation following orchiectomy
patient reliability for F/U
absence of marker elevation postorchiectomy
30% recurrence
high risk of recurrence: preorchiectomy AFP more than
80ng/ml and a slower than usual decrease in AFP after
orchiectomy
Mixed germ cell tumors (6)
treatment of NSGCT
High risk group: 11 criteria
lymphovascular permeation
advanced local tumor stage
EC, predominant or unassociated with teratoma
EC volumne>2ml
teratomatous componentfull course C/T ); or,
limited course, adjuvant therapy
Case with advanced-stage (bulky retroperitoneal
disease or distant metastasis) --->cisplatin-base C/T +
surgical resection
Mixed germ cell tumors (9)
prognosis
Presence of some elements appears to modify
the behavior of other components:
A teratomatous component in conjunction with
embryonal carcinoma(EC) significantly lowers
metastatic rate compared to pure EC.
Presence of yolk sac tumor elements has also been
associated with a lesser tendency to metastasize.
Mixed germ cell tumors (10)
prognosis of NSGCT
Prognostic factors:
extent of disseminated disease
degree of elevation of serum markers
adverse prognostic features: ---increasing age
presence of liver, bone, or brain metastasis
AFP>1000IU/L or beta-hCG>10000IU/L
a mediastinal mass >5cm
20or more lung metastases
absence of EC or fibrous tissue component
Prognosis of NSGCT (11)
5-year survival rate
1950s:
60%: testicular GCT
30%: testicular nonseminomatous GCT
The current survival rate for patients with
nonseminomatous GCTs is in excess of 90%.
Combination of effective, multiagent C/T with
surgery markedly increases survival.